Biochemical and genetic studies of mutant cell cultures which are resistant to the effects of 25-hydroxycholesterol will be carried out in an effort to define the nature of the mutations. The nature and function of cytoplasmic proteins which bind 25-hydroxycholesterol in human leukemia cell cultures and in mouse and hamster cell lines will be investigated. An effort will be made to develop an assay for the binding proteins which can be applied to tumors and cells in vivo. The ability of various sterols to substitute for cholesterol in the membranes of growing cell cultures will be studied. The biosynthesis of dolichol in cell cultures and in various normal and malignant tissues in vivo will be investigated.